Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease in which 50% of patients die within 30 months of onset. Some 10% of cases are familial, and mutations in copper/zinc ion-binding superoxide dismutase 1 (SOD1), repeat expansions in the C9orf72 gene, and mutations in fused-in-sarcoma (FUS) comprise as many as 75% of them. C9orf72 expansions also account for approximately 15% of sporadic ALS cases. A mouse model overexpressing human mutant SOD1 G93A recapitulates many features of the disease, such as motor neuron degeneration and early death. However, the vast majority of ALS cases are not due to SOD1 mutations, and the relevance of animal model to these sporadic ALS patients remains unclear. Creating human motor neurons via stem cell technology now offers an opportunity to study the properties of human motor neurons derived from ALS patients, and thereby disease pathology, in both familial and sporadic ALS cases as well as to provide a means to screen for drugs that may treat or reduce a risk of developing the disease.